TPM2
Chr 9tropomyosin 2
Also known as: AMCD1, CMYO23, CMYP23, DA1, DA2B, DA2B4, HEL-S-273, NEM4
Beta-tropomyosin is an actin filament binding protein primarily expressed in slow, type 1 muscle fibers that regulates muscle contraction. Mutations cause autosomal dominant congenital myopathies including cap disease and nemaline myopathy, as well as distal arthrogryposis syndromes types 1A and 2B4. The pathogenic mechanism involves altered expression of other sarcomeric tropomyosin proteins through a dominant-negative effect.
Definitive — sufficient evidence for diagnostic panels
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TPM2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools